Poly-4-hydroxybutyrate (P4HB) and copolymers thereof can be produced using transgenic fermentation methods, see, for example, U.S. Pat. No. 6,548,569 to Williams et al., and are produced commercially, for example, by Tepha, Inc. (Lexington, Mass.). Poly-4-hydroxybutyrate (P4HB, TephaFLEX® biomaterial) is a strong, pliable thermoplastic polyester that, despite its biosynthetic route, has a relatively simple structure.

The polymer belongs to a larger class of materials called polyhydroxyalkanoates (PHAs) that are produced by numerous microorganisms (see, for example, Steinbüchel A., et al. Diversity of Bacterial Polyhydroxyalkanoic Acids, FEMS Microbial. Lett. 128:219-228 (1995)).
U.S. Pat. Nos. 6,245,537, 6,623,748 and 7,244,442 describe methods of making PHAs with little to no endotoxin, which is suitable for medical applications. U.S. Pat. Nos. 6,548,569, 6,838,493, 6,867,247, 7,268,205, and 7,179,883 describe use of PHAs to make medical devices. Copolymers of P4HB include 4-hydroxybutyrate copolymerized with 3-hydroxybutyrate or glycolic acid (U.S. patent application No. 2003/0211131 by Martin and Skraly, U.S. Pat. No. 6,316,262 to Huisman et al., and U.S. Pat. No. 6,323,010 to Skraly, et al.). Methods to control molecular weight of PHA polymers have been disclosed by U.S. Pat. No. 5,811,272 to Snell et al.
PHAs with controlled degradation and degradation in vivo of less than one year are disclosed by U.S. Pat. Nos. 6,548,569, 6,610,764, 6,828,357, 6,867,248, and 6,878,758 to Williams, et al. and WO 99/32536 to Martin, et al. Applications of P4HB have been reviewed in Williams, et al., Polyesters, III, 4:91-127 (2002), and by Martin, et al. “Medical Applications of Poly-4-hydroxybutyrate: A Strong Flexible Absorbable Biomaterial”, Biochem. Eng. J. 16:97-105 (2003). Medical devices and applications of P4HB have also been disclosed by WO 00/56376 to Williams, et al. Several patents including U.S. Pat. Nos. 6,555,123, 6,585,994, and 7,025,980 describe the use of PHAs in tissue repair and engineering.
In the practice of surgery there currently exists a need for absorbable non-wovens with improved performance. These non-wovens can be used, for example, for soft tissue repair, to reinforce tissue structures, to separate tissues, and to serve as tissue engineering scaffolds, including guided tissue regeneration scaffolds. They may also be used as components of other devices. A number of other absorbable materials have been used to produce non-wovens for use in surgery. For example, non-wovens have been made from polyglycolic acid (PGA) or copolymers containing lactic acid. These materials do not, however, have ideal properties for many procedures and applications. Non-wovens made from polyglycolic acid breakdown too rapidly for many applications, and release acidic degradation products that can cause inflammatory reactions.
WO 04/101002 to Martin et al. discloses monofilament and multifilament knitted meshes of P4HB, produced by knitting monofilament and multifilament fibers of P4HB. WO 09/085823 to Ho, et al. discloses medical devices containing melt-blown non-wovens of poly-4-hydroxybutyrate and copolymers thereof. U.S. Pat. No. 8,287,909 discloses non-wovens of poly-4-hydroxybutyrate derived by a continuous melt-blown process. Notably, the process of melt blowing can limit the utility of this method to produce non-wovens, particularly when it is necessary to produce three-dimensional non-woven fabrics and devices, and apply coatings of non-wovens on scaffolds or other materials. The process of melt extrusion causes a dramatic loss in the molecular weight of the polymer such that the molecular weight of the polymer in the melt blown non-woven is substantially less than in the polymer feed. The lower molecular weight of melt blown non-woven is a particular disadvantage when it is desirable to retain mass and/or mechanical properties, such as burst strength, in vivo, for a prolonged period of time, since lower molecular weight P4HB non-wovens degrade faster in vivo than higher molecular weight P4HB non-wovens. U.S. Publication No. 2012/0150285 by Cahil, et al. discloses a continuous process for making dry spun non-wovens, including non-wovens of P4HB. The non-wovens are collected on a stationary plate.
There is still a need for non-wovens of P4HB, with improved mechanical properties, which retain the higher molecular weight of the starting material, burst strength, and degradation kinetics.
It is an object of the present invention to provide methods to produce dry spun non-wovens of absorbable P4HB and copolymers thereof with improved mechanical properties, and without substantial loss of the polymer molecular weight during processing.
It is another object of the present invention to provide dry spun non-wovens which are biocompatible and can be used in medical applications, for example, as implants such as devices for soft tissue repair, replacement, and regeneration, temporary tissue support, tissue separation, as well as devices or components of devices for tissue in-growth (or guided tissue regeneration) and tissue engineering.
It is therefore an object of the invention to provide continuous processes for dry spun non-woven production, which can be incorporated into or formed into medical devices with excellent physical and mechanical properties for medical applications.